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Biomedical subjects

R H Waldman

Publications and source records attributed to R H Waldman.

At least 19 recordsLinked to original sources

Pulmonary histoplasmosis associated with exploration of a bat cave.

Approximately 14 days after exploring a limestone cave in northcentral Florida in February 1973, an 18-year-old female developed a respiratory illness with pronounced shortness of breath and cyanosis. The following day, an 18-year-old male presented to the hospital with similar complaints. The association of illness with their recent caving experience prompted further epidemiologic investigation. Twenty-nine members of a church-sponsored youth group explored the implicated cave. Twenty-three of them later became ill with complaints of cough, afternoon fever and sweats, chest discomfort, and dyspnea on exertion. Histoplasmin skin tests were positive in 18 of 24 individuals tested. Serum for complement fixation (CF) was positive in 12 of 26. Testing of area residents revealed a low incidence of skin test and CF positivity (7% and 0%, respectively). That spelunkers are at risk of acquiring pulmonary histoplasmosis has been noted previously; in Florida this has been related to the exploration of caves infested with bats. This is the largest reported outbreak of acute pulmonary histoplasmosis that has been associated with spelunking and further points out that only those individuals who enter the cave are at risk of acquiring the disease, and not those who reside in the surrounding area.

Adolescent

Gastroenteritis: etiology, pathophysiology and clinical manifestations.

The infectious etiologic agents of gastroenteritis are manifold and have only recently been studied in greater depth. Part of the problem in studies pertaining to diarrhea is the difficulty in identifying fecal "pathogens" among an enormous number of indigenous fecal microorganisms. Finally, the recognition of the pathogenicity of enterotoxins has created an awareness of the complexity of gastrointestinal physiology with host-parasite interactions.

Animals

Lack of effect of an interferon inducer, N,N-dihexadecyl-m-xylylenediamine, on rhinovirus challenge in humans.

CP-28,888-27 and placebo nasal sprays were compared in 62 normal volunteers challenged with rhinovirus type 13 or 21 in two randomized, double-blind studies. Half of the subjects received CP-28,888-27 and half received nasal placebo administered at 24, 20, and 16 h before challenge and 4 and 8 h after challenge. In each study, the number of subjects shedding virus in nasal washes, the number developing fourfold or greater serum antibody responses, and the number developing afebrile or febrile upper respiratory tract illness were not significantly different comparing subjects given CP-28,888-27 and those given placebo. Interferon was detected in nasal washes from 5 of 15 volunteers tested in the CP-28,888-27 group compared to 2 of 15 volunteers from the placebo group.

Adult

Guinea pig lung lavage cells after intranasal BCG sensitization.

Recent studies have suggested that intranasal administration of antigen can induce local cell-mediated immunity in lung lavage cells. The present study was designed to examine the changes in composition of lung lavage cells and their capacity to produce the lymphokine migration inhibitory factor after intranasal immunization with BCG in guinea pigs. Results indicate that guinea pigs responded to respiratory tract BCG infection with an increase in immunocompetent cells in the bronchoalveolar tract and with production of migration inhibitory factor. After local pulmonary BCG administration, the total number of cells increased as compared with that of the uninfected animals, the increase being statistically significant within 2 weeks. This marked increase in the total cell population is due to a more than doubling of the number of macrophages in the lavage fluid. Animals also developed at this time positive delayed hypersensitivity to intradermally administered purified protein derivative. A significant increase in the total lymphoid cells and macrophage population was observed again at 6 weeks after sensitization, suggesting that the response is biphasic in nature. At 6 weeks, however, there was also a significant rise in total lymphocytes and T cell population in addition to macrophage numbers. This increase in T cells correlated with an increase in production of migration inhibitory factor in the presence of purified protein derivative. These data suggest that the immune response of the respiratory tract after BCG challenge involves increased recruitment of immunocompetent cells locally at the site of infection and that these cells are capable of producing effector molecules in terms of the elaboration of migration inhibitory factor.

Animals

Studies on oral adjuvants against murine salmonellosis.

1) Attempts were made to develop oral adjuvants against murine salmonellosis. 2) Streptomycin, levamisole and PHA show potential immunoenhancing properties against salmonella infection. 3) The mode of action of these agents remain to be elucidated. Observed results of PHA enhancement may be related to its blastogenic effects in the splenic T-cells. 4) Decrease in certain bacterial flora resulting in less antigenic competition may be the mode of action of streptomycin as adjuvant when added to oral salmonella vaccine.

Adjuvants, Immunologic

Effect of CP-20,961, an interferon inducer, on upper respiratory tract infections due to rhinovirus type 21 in volunteers.

Topically administered CP-20,961 is known to stimulate nasal interferon. Studies in volunteers given the drug prior to challenge with rhinovirus have yielded both fairly good results and only fair or poor results. This study was undertaken in an attempt to settle the differences between the results of these trials and to evaluate the possible effectiveness of CP-20, 961 when given after virus challenge. Sixty volunteers were randomly divided into four groups. One group received placebo, the second received the drug on the day before and the day of challenge, the third was given the drug for two days beginning 24 hr after challenge, and the fourth received the drug for two days beginning 48 hr after challenge. The average number and severity of symptoms in the group that received CP-20,961 prior to challenge were about half of those in the control group. There was no decrease, however, in the number and severity of symptoms in the groups that received the drug after challenge.

Adolescent

Protective studies with group A streptococcal M protein vaccine. III. Challenge of volunteers after systemic or intranasal immunization with Type 3 or Type 12 group A Streptococcus.

Alum-precipitated and soluble, purified M protein vaccines were prepared from type 3 and type 12 group A Streptococcus. Adult volunteers were assigned to one of three groups: group I received placebo by both parenteral and intranasal routes; group 2 received vaccine parenterally (either type 3 or type 12) and placebo intranasally; and group 3 received placebo parenterally and vaccine intranasally (either type 3 or type 12). Subjects were inoculated three times at montly intervals. Thirty to 50 days after the last dose, all subjects were challenged with homologous streptococci applied to the oropharynx. Six subjects (30%) vaccinated subcutaneously had definite illness, three (15%) had probable illness, and 11 (55%) had no illness. In the group vaccinated intranasally, four (14%) had definite illness, two (7%) had probable illness, and 22 (79%) had no illness. Fifteen controls (42%) had definite illness, and 21 (58%) had no illness. The rate of colonization was significantly lower in recipients of intranasal vaccine. Average clinical scores and vaccine side effects were also decreased in subjects vaccinated intranasally. Induced serum antibody as measured by passive hemagglutination was not a reliable predictor of resistance to streptococcal pharyngitis. Penicillin was administered to all subjects five days after challenge. No sequelae of streptococcal infection or other complications occurred. Thus, local immunization with M protein apparently may reduce both colonization and clinical illness after challenge with homologous streptococci.

Administration, Intranasal

Therapeutic efficacy of inosiplex (Isoprinosine) in rhinovirus infection.

Inosiplex (Isoprinosine), the paracetamidobenzoic acid salt of inosine dimethylaminoisopropanol, has shown antiviral activity in cell culture and in animals. Controlled challenge studies using the drug in a prophylactic fashion, however, have been disappointing. In vitro studies, as well as uncontrolled clinical trials, have suggested that the drug might be more effective when used therapeutically. We therefore undertook to test inosiplex in a controlled, double-blind, therapeutic study of volunteers challenged with rhinovirus. Thirty-nine volunteers were randomly divided into groups receiving either inosiplex or placebo tablets. Drug or placebo was started either at the time of, or 48 hours after challenge with rhinovirus Type 21. Illness was assessed in terms of the classical common cold symptoms, and infection was also determined by viral isolation from daily nasal wash specimens and by serum antibody rises. Five of 19 volunteers in the inosiplex group became ill, whereas 14 of 20 in the placebo group were sick (p less than 0.01). There was no difference between the control and inosiplex groups in the number of volunteers from whom rhinovirus was isolated. There was, however, a reduction in the duration of virus shedding in the inosiplex group. Seroconversion was also slightly less common in the inosiplex group. Immunologic studies suggest that inosiplex stimulates the lymphocyte mitogenic response. The results suggest that inosiplex exerts significant therapeutic benefits in rhinovirus infection.

Adult

An attenuated influenza virus vaccine: protection against homologous and heterologous strains of virus.

An effective influenza virus vaccine should be capable of inducing protection against both the homologous strain of virus and the heterologous strains representing antigenic drift. For evaluation of the protection provided by an attenuated influenza virus vaccine, volunteers were immunized intranasally with either placebo or influenza A/England/42/72 (H3N2) virus vaccine in a double-blind fashion in two doses administered two weeks apart. Forty-seven subjects were challenged 30-100 days after the second dose with either the homologous or a virulent heterologous strain of virus [A/Dunedin/73 (H3N2)]. The vaccine resulted in good clinical protection against challenge with both the homologous and heterologous strains of virus. The rates of protection against infection (as judged by antibody responses, irrespective of signs and symptoms) were also good (72% and 60% against the homologous and heterologous strains, respectively). Thus, immunity induced by this attenuated influenza virus vaccine extends to provide protection against a related but nonidentical influenza virus.

Adolescent

Nonspecific protection of mice against influenza virus infection by local or systemic immunization with Bacille Calmette-Guérin.

Bacille Calmette-Guérin (BCG) has been used effectively to protect nonspecifically against bacterial infections and neoplasms, probably by enhancement of cell-mediated immunity. It has been suggested that cell-mediated immunity plays a role in the host defense against certain viral infections. In recent in vitro studies, macrophages from animals sensitized by BCG were more effective in lowering the titer of influenza virus than were macrophages from control animals. The purpose of this study was to investigate the in vivo effectiveness of nonspecific immune stimulation with BCG on influenza virus infection in mice. Immunization with BCG resulted in significant protection of mice. Also, the local (nasal) route of immunization was more effective than the systemic (intraperitoneal) route against the intranasal inoculum of virus, a finding which suggests that important role of local immunity, i.e., either earlier stimulation of secretory antibody or nonspecific cell-mediated immunity. The time course of the resistance ot infection suggests that interferon was not the protective mechanism.

Administration, Intranasal